Trends in morbidity and mortality of hepatic resection for malignancy. A matched comparative analysis.

OBJECTIVE: The authors define more clearly the trends in morbidity and mortality after hepatic resection for malignant disease in matched patient groups during two discrete time periods. SUMMARY BACKGROUND DATA: Recent reports have shown improvement in operative morbidity and mortality associated with hepatic resection; however, results often included resections for benign disease and trauma. Furthermore, specific factors contributing to the improvement in operative risks between the last two decades have not been defined. METHODS: A retrospective matched comparative analysis was conducted of patients with primary and metastatic hepatic malignancy resected with curative intent between two periods (1976 to 1980 and 1986 to 1990). Eighty-one patients met our inclusion criteria in the early period; this group was matched with 81 patients from the latter period by the following four parameters: age, gender, type of malignant disease, and extent of resection. Records of these two patient groups were abstracted for clinical presentation, co-morbid factors, operative techniques, and perioperative morbidity and mortality. RESULTS: The authors found a significant decrease in operative morbidity, median perioperative transfusion, and length of hospital stay in the latter period (1986 to 1990). The incidence of postoperative subphrenic abscess and intra-abdominal hemorrhage was significantly lower during this period. Operative mortality rate was similar for both periods, 4.9% and 1.2%, respectively (p > 0.05). CONCLUSION: Hepatic resection for malignant disease currently can be performed with a low morbidity and mortality in the hands of trained and experienced hepatic surgeons; operative risks of hepatic resection should not deter its application in the treatment of primary and metastatic malignant disease of the liver.

Perioperative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma.

The authors reviewed their institutional experience with liver resection for metastatic colorectal carcinoma to (1) determine whether perioperative blood transfusion affects survival; (2) identify prognostic determinants; and (3) estimate the patient requirement for a prospective randomized trial designed to demonstrate efficacy of liver resection. Two hundred eighty consecutive patients treated by potentially curative liver resection between 1960 and 1987 were included. Data were obtained for all but 10 patients for at least 5 years after operation or through 1990. Actuarial survival curves related to potential prognostic determinants were analyzed with the log-rank test. Overall, survival was 47 +/- 3% at 3 years and 25 +/- 3% at 5 years, including 4% 60-day operative mortality rate. Eighty-one patients who did not receive blood 7 days before to 14 days after operation had 60 +/- 6% 3-year and 32 +/- 6% 5-year survival compared with 40 +/- 4% and 21 +/- 3% survival rates for 183 patients who received at least one unit (p = 0.03, operative deaths excluded). Extrahepatic disease (p = 0.015), extrahepatic lymph node involvement (p = 0.002), satellite configuration of multiple metastases (p = 0.0052), and initial detection by abnormal liver enzymes (p = 0.0005) were associated with poor survival rates. Synchronous presentation of metastatic and stage B primary disease was associated with a favorable prognosis (p = 0.003). The requirement for a prospective randomized trial estimated by an exponential survival model would be 36, 74, 168, or 428 patients if 5-year survival without resection were 1, 5, 10, or 15%. We conclude that (1) perioperative blood transfusion may be adversely associated with survival; (2) extrahepatic disease, extrahepatic lymph node involvement, satellite configuration, and initial detection by clinical examination or a liver enzyme abnormality portend a poor prognosis; and (3) a prospective randomized trial of liver resection is impractical because of the large patient requirement, at least by a single institution.

Intrahepatic cholangiocarcinoma: clinical aspects, pathology and treatment.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary tumor of the liver. To further define its clinicopathology and surgical management, we reviewed our experience. Clinical presentations of 32 patients with ICC was similar to that with hepatocellular carcinoma. Jaundice occurred in only 27 percent. ICC was unresectable due to advanced disease stage in 81 percent. Six patients had curative resections with two 5 year disease free survivors. Underlying liver disease was associated with ICC in 34 percent of patients.

Carcinoma of the gallbladder. Does radical resection improve outcome?

The records of 111 patients with gallbladder carcinoma operatively treated between 1972 and 1984 were retrospectively reviewed. Fifty-seven percent of patients had distant metastases; another 16% had nodal metastases without distant disease. Median survival was 0.5 years, and 5-year survival was 13%. Clinical jaundice, tumor stage, and tumor grade were all predictive of patient outcome. DNA ploidy, measured in 70 patients, was not a prognostic indicator. In 36% of patients, cholecystectomy (20%) or radical cholecystectomy (16%), which included adjacent liver and regional lymph node resection, was potentially curative. Median survival for patients undergoing radical procedures was 3.6 years, and survival was 0.8 years for patients following cholecystectomy. The 5-year survival rates were comparable (33% vs 32%). While radical cholecystectomy may benefit individual patients and can be accomplished with low morbidity, there was no overall survival advantage compared with cholecystectomy.

Primary hepatic malignancy: surgical management and determinants of survival.

To further define the clinicopathologic features and determinants of survival, we reviewed the cases of 110 patients with primary hepatic malignancy managed surgically between 1975 and 1986. Presenting signs of symptoms were pain (57%), fatigue (48%), abdominal mass (40%), and weight loss (33%). Twenty-six percent of patients had a history of hepatitis or cirrhosis. Histopathologically, tumors were hepatocarcinoma (72%), fibrolamellar variant (7%), cholangiocarcinoma (9%), mixed (7%), and other (5%). Resectability rate with curative intention was 67%. Exploration and biopsy alone was performed in 27% and palliative resection in 6%. Hospital mortality was 9%, and serious morbidity was 22%. Perioperative morbidity and mortality were significantly associated with operative blood loss. Median survival was 12.6 months, with a 5-year survival of 18%. Median survival after curative resection was 22.8 months, and 5-year survival was 27%. Univariate analysis showed that female sex, normal performance status, well-differentiated tumor, and curative resection were associated with increased survival; cholangiocarcinoma, nodal metastases, cirrhosis, hypocalcemia, prolonged prothrombin time, and increased serum transaminase and alkaline phosphatase were associated with decreased survival. Cox multivariate analysis showed that curative resection, normal performance status, and well-differentiated tumors were associated with increased survival, and prolonged prothrombin time and hypocalcemia were associated with decreased survival.

Is proximal pancreatoduodenectomy with pyloric preservation superior to total pancreatectomy?

The records of all patients who underwent pylorus-preserving pancreatic resection (29 subtotal and 4 total pancreatectomies) during a 10-year period at the Mayo Clinic were reviewed. Thirty-day operative mortality was 6%. Early postoperative morbidity occurred in 45% of patients and necessitated reoperation in four patients. One patient had a hemorrhage from a marginal ulcer in the early postoperative period. The incidence of late postoperative morbidity was 18%. Marginal ulcers developed in the late postoperative period in three additional patients, for an overall incidence of 13%. One patient underwent vagotomy and pyloroplasty because of intractable bleeding 2 years after initial operation. The 29 patients who underwent pylorus-preserving pancreatoduodenectomy (PPW) were compared (retrospectively) with 200 patients who had undergone standard pancreatoduodenectomy (Whipple operation) during the same 10-year period. The overall incidences of marginal ulcer were 10% in the PPW group and 5% in the Whipple group; the incidences of delayed gastric emptying were similar in these groups. We believe that caution is warranted in the use of PPW, as yet an unproved procedure.

Hepatoma in the noncirrhotic liver.

The pathologic features, clinical presentation and natural history of hepatocellular carcinoma (HCC) developing in the noncirrhotic liver were studied in 61 patients against a background of 63 patients seen concurrently with HCC complicating cirrhosis. Noncirrhotic HCC had a bimodal age distribution, with females predominating the first age-clustering (10-50 years) and males predominating the second age-clustering (50-90 years). Cirrhotic HCC had a unimodal age distribution (40-90 years) with male dominance throughout. Estrogen exposure was noted in 57% of the noncirrhotic HCC women overall and in 80% of those in the younger age-clustering. The majority of noncirrhotic HCC presented with a single hepatic mass or a dominant primary with satellite lesions in contrast to the usual multinodular or diffuse disease seen with cirrhosis. Twenty-nine noncirrhotic patients survived complete resection of disease limited to the liver and exhibited a median survival of 2.7 years with a 5-year survival of 25%. Low histologic grade, minimal necrosis, and the absence of hemoperitoneum, hepatomegaly, and adjacent organ involvement were all favorable prognostic variable. Patients with metastatic or locally unresectable noncirrhotic HCC had a median survival of 9 months, and 24% survived in excess of 2 years. This survival experience is significantly more favorable than cirrhotic HCC patients, who had only a 1.2-month median and a 3% 2-year survival. Low histologic grade, mild mitotic activity and the presence of some fibrosis within the specimen were associated with a favorable outcome in advanced noncirrhotic HCC. The favorable prognosis and heterogeneous composition of the noncirrhotic, when compared to the cirrhotic HCC cohort, may be important considerations in the design and evaluation of future clinical trials.

Surgical management of chronic pancreatitis: long-term results in 141 patients.

The management of pancreatic pain is a controversial subject and the treatment recommended varies from one extreme to the other. Some authorities advise simply waiting for chronic pancreatitis to 'burn out', while others practise removal of the entire gland. In this paper we present 141 patients who underwent surgery for chronic pancreatitis at the Mayo Clinic. The main indication for operation was pancreatic pain and the choice of operation was based on anatomical abnormalities in the gland. The long-term results of the policy are reviewed (mean follow-up 8.5 years). Length of history, aetiology of disease, pancreatic dysfunction and pathology, time after operation and continued alcohol abuse were computer analysed for a statistically significant influence on pain relief, ability to work, pancreatic function and survival. There was one operative death (mortality rate 0.7 per cent). Continued drinking was not shown to affect postoperative pain relief but 10-year survival was significantly less in alcoholics than in those with non-alcoholic pancreatitis (P less than 0.02). Dilated ducts and duct calculi were associated with good results for pain relief although this association did not achieve statistical significance. Parenchymal calcification and time after operation did not influence the results of surgery. When the operation failed to relieve pain, spontaneous remission occurred in a few cases only. Seventy-seven per cent of patients had lasting relief of pain and operations selected on the basis of gross pathology were equally effective in relieving pain. Longitudinal pancreaticojejunostomy in those with dilated ducts and a Whipple operation for disease of the pancreatic head gave good results.(ABSTRACT TRUNCATED AT 250 WORDS)

Resection of the liver for colorectal carcinoma metastases. A multi-institutional study of long-term survivors.

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primary carcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized.

Prognostic significance of nuclear deoxyribonucleic acid ploidy patterns in resected hepatic metastases from colorectal carcinoma.

Nuclear deoxyribonucleic acid (DNA) ploidy studies of paraffin-embedded archival tumor specimen blocks were performed by flow cytometry on extracted nuclei from 101 surgically resected hepatic metastases from colorectal cancer. In 28 patients, the corresponding primary carcinoma of the metastases was also studied. Tumor clinicopathology and clinical course of the patients were reviewed. Preparation of paraffin-embedded tissue specimens was performed by the technique of Hedley et al. and stained with propidium iodide according to the method of Vindelov et al. Eighty-eight of 101 metastatic tumors and 26 of 28 primary tumors yielded evaluable DNA histograms. Twenty-six metastases showed a DNA diploid pattern, 25 showed a significantly increased 4C peak (DNA tetraploid/polyploid), and 37 had a DNA aneuploid peak. Ploidy pattern was constant between primary and metastases in 84.6% of tumors. No significant relationship between host and tumor characteristics and ploidy pattern was found except for a correlation between grade 3 metastases and DNA aneuploid. Survival of patients with DNA aneuploid metastases was significantly less than that of patients with DNA diploid metastases (p = 0.03). However, among DNA nondiploid metastases, survival was significantly less for low DNA index metastases (less than or equal to 1.5) than for high DNA index (greater than 1.5) metastases (p less than 0.05). Flow cytometric DNA ploidy measurements may have prognostic value for patients with resected hepatic metastases from colorectal carcinoma.

Diagnosis and treatment of jaundice.

1. CT and sonography are helpful in distinguishing between an obstructing lesion and hepatocellular disease as the cause of jaundice. 2. CT and sonography can demonstrate the level and extent of an obstructing lesion, and can define its nature if a mass more than 1-2 cm is present; sonography is usually the preferred screening study because of its availability, relatively low cost and lack of radiation hazard. 3. PTC or ERCP is useful in the evaluation of jaundice when sonography and CT are equivocal, fail to provide information necessary to establish proper therapy, or are at variance with the clinical impression of obstructive jaundice; in addition to defining obstructions these techniques can detect atrophy, sequestra, stones, abscesses, fistulas, primary sclerosing cholangitis, etc. 4. PBD offers an expedient alternative to surgical decompression in patients with obstructive jaundice, since most cancers that cause biliary obstruction are not resectable for cure at the time of diagnosis.

Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence.

The Registry of Hepatic Metastases has collected data on consecutive patients from 24 institutions who have undergone hepatic resection for colorectal carcinoma metastases. Patterns of recurrence were examined in a subgroup of 607 patients who had undergone curative resection of isolated hepatic metastases. Forty-three percent of these patient have had recurrences in the liver and 31% have had recurrences in the lung (either alone or in combination with other organs). A multivariate analysis showed that patients with positive pathologic margins or bilobar metastases were at an increased risk of having a recurrence in the liver (68% and 64%, respectively). We conclude that: hepatic resection effectively controls hepatic tumor in a substantial number of patients, adjuvant therapy after hepatic resection should be directed at both the lung and liver to significantly increase survival, and patients with positive pathologic margins or bilobar metastases are at an increased risk for hepatic recurrence.

Mass lesions of the liver.

Each of the six most common mass lesions of the liver may vary with respect to pathogenesis, clinical manifestations, natural history, usefulness of diagnostic tests, and the need for and value of surgical treatment. Despite these many variables, one broad generalization can be made: three lesions (cysts, cavernous hemangiomas, and focal nodular hyperplasia) usually are incidental findings that can be ignored, whereas three other tumors (adenomas, malignant hepatomas, and metastatic lesions) involve a threat to life that may be modified by surgical removal. This generalization, however, is not a guide to specific management because exceptions, atypical manifestations, diagnostic difficulties, and variations in the risks and limitations of surgical therapy are so common. The widespread use of new techniques for "imaging" has changed the responsibility of both the medical and the surgical hepatologist. Lessons of the past learned from the management of clinically evident symptomatic lesions have little usefulness in the management of small, "early," or indeterminate lesions. In these circumstances, physicians, surgeons, and radiologists must work in concert when a lesion is first found. Only then will clinically relevant tests be done that will ensure proper treatment of the patient.

Focal nodular hyperplasia and hepatic adenoma: comparison of angiography, CT, US, and scintigraphy.

The authors reviewed 23 cases of focal nodular hyperplasia and 13 cases of hepatic adenoma, all of which were confirmed pathologically. All solitary masses that exhibited normal or increased uptake of technetium 99m-sulfur colloid were shown to be hyperplasia; while previous criteria such as a central blood supply on angiograms or a central scar on computed tomography (CT) or ultrasound (US) scans were helpful, they were relatively infrequent. A mass that was slightly hypodense and homogeneous on a CT or US scan and highly vascular with an intense capillary stain on an angiogram was almost always hyperplasia. Acute hemorrhage within a focal hepatic tumor was common in adenoma but did not occur in hyperplasia.

Postoperative reflux gastritis: pathophysiology and long-term outcome after Roux-en-Y diversion.

Sixteen patients with clinical features of postoperative gastritis who had been advised to have a Roux-en-Y diversion were studied prospectively. Studies were done pre- and postoperatively (mean follow-up, 4.9 years; range, 3.8 to 6.9), and the findings were compared with those in 11 control subjects with previous enterogastric anastomosis but with no symptoms. The patients had higher concentrations of bile acids and trypsin in gastric samples than did controls. Patients had greater endoscopic changes, although mucosal histologic characteristics were similar in both groups. Administration of aluminum hydroxide or cholestyramine reduced the aqueous concentrations of bile acids in gastric contents. Roux-en-Y diversion virtually eliminated duodenogastric reflux, and gastroscopic appearances returned to normal. However, Roux-en-Y diversion did not change mucosal histologic characteristics. Symptom scores were reduced in the early postoperative period, but bilious vomiting was the only symptom alleviated consistently and permanently. As a treatment for postoperative gastritis, Roux-en-Y diversion offers potential but limited benefits.

Clinical trial of adjuvant chemotherapy after surgical resection of colorectal cancer metastatic to the liver.

Adjuvant chemotherapy consisting of 5-fluorouracil and semustine was given to 26 patients who had undergone resection (with curative intent) of hepatic metastatic lesions from a primary colorectal carcinoma. Our objective was to obtain preliminary observations regarding the effectiveness of this regimen for improving the long-term survival associated with hepatic resection alone in these patients (the overall 5-year survival after hepatic resection is 25% at our institution). At the time of analysis, the malignant disease had progressed in 19 of our patients, and 17 patients had died. For all patients who receive adjuvant chemotherapy, the median duration of survival is 34 months, and the estimated 5-year survival is 15%. Statistical analysis indicated no significant advantage in survival for the study patients in comparison with 26 control patients who were treated with hepatic resection only and were closely matched for prognostic factors. Because 5-fluorouracil plus semustine conferred no apparent beneficial effects as an adjuvant treatment in this exploratory study, we do not recommend a definitive randomized trial of this regimen.